Multiphasic Organization and Differential Dynamics of Proteins Within Protein-DNA Biomolecular Condensates

Biomolecular condensates formed through liquid-liquid phase separation are increasingly recognized as critical regulators of genome organization and gene expression. While the role of proteins in driving phase separation is well-established, how DNA modulates the structure and dynamics of protein-DNA condensates remains less well understood. Here, we employ a minimalist coarse-grained model to investigate the interplay between homotypic protein-protein and heterotypic protein-DNA interactions in governing condensate formation, composition, and internal dynamics. Our simulations reveal that DNA chain length and flexibility critically influence condensate morphology, leading to the emergence of multiphasic and core-shell organizations under strong heterotypic interactions. We find that DNA recruitment into the condensate significantly alters protein mobility, giving rise to differential dynamics of proteins within the condensate. By analyzing the distribution profiles of protein displacements, we identify up to five distinct diffusion modes, including proteins bound to DNA, confined within the dense phase, or freely diffusing. These results provide a mechanistic framework for interpreting spatially heterogeneous protein dynamics observed in chromatin condensates and emphasize the direct role of DNA in tuning condensate properties. Our findings provide new insights into how biophysical parameters may control the functional architecture of protein-DNA condensates in biological systems. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/658691v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@108a818org.highwire.dtl.DTLVardef@153f9a1org.highwire.dtl.DTLVardef@29f220org.highwire.dtl.DTLVardef@1d74d6e_HPS_FORMAT_FIGEXP M_FIG C_FIG